title: Risk factors for liver injury with an elevated serum bilirubin concentration caused by antituberculous drugs.
abstract: OBJECTIVE
  No studies have so far sufficiently investigated the risk factors for drug-induced liver injury (DILI) with an elevated serum bilirubin concentration.
  
  
  METHODS
  We conducted a historical cohort study observing inpatients admitted to two hospitals in Japan. A decreased level of activities of daily living (ADL) was defined as a Barthel Index score of <80. The patients were treated with standard regimens under a directly observed treatment short-course strategy.
  
  
  RESULTS
  The cohort of 356 patients comprised 244 men (68.5%) and 112 women (31.5%), with a mean age of 63.8±20.2 years. Compared with the patients who did not experience DILI with a bilirubin level of ≥2.0 mg/dL, the patients who experienced DILI with a bilirubin level of ≥2.0 mg/dL more often had a decreased level of ADLs, were more likely to suffer from chronic cardiac disease, had lower serum albumin levels and were less often treated with four-drug regimens involving pyrazinamide (PZA). In a logistic regression analysis in which these five factors acted as independent variables, a decreased level of ADLs was the strongest predictor for DILI with a bilirubin level of ≥2.0 mg/dL, with an odds ratio of 16.5 (95%CI: 1.7-159; p=0.015), followed by chronic cardiac disease, with an odds ratio of 4.0 (95%CI: 1.2-12.6; p=0.020).
  
  
  CONCLUSIONS
  A decreased level of ADLs and chronic cardiac disease are strong risk factors for DILI with a bilirubin level of ≥2.0 mg/dL resulting from the use of antituberculous drugs. Physicians should pay close attention to the possibility of DILI with a bilirubin level of ≥2.0 mg/dL when treating tuberculosis patients with a decreased level of ADLs and/or chronic heart disease.
authors.affiliation: Department of Internal Medicine and Clinical Immunology, Yokohama City University Graduate School of Medicine, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kato
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Horita
authors.forename: Naoki
authors.initials: N
authors.lastname: Miyazawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Yoshiyama
authors.forename: Atsuhisa
authors.initials: A
authors.lastname: Ueda
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ishigatsubo
mesh_terms: D000203:Activities of Daily Living; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000995:Antitubercular Agents / Q000009:adverse effects*; D001663:Bilirubin / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D015331:Cohort Studies; D005260:Female; D006331:Heart Diseases / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
chemical_list: D000995:Antitubercular Agents; D015415:Biomarkers; D001663:Bilirubin